Bimekizumab Treatment Resulted in Rapid Response That Was Associated with Clinically Important Improvements in Patient-Reported Outcomes up to 3 Years in Patients with Psoriatic Arthritis

Author(s):

Laure Gossec, ¹ Dafna D. Gladman,² M. Elaine Husni,³ Tadashi Okano,⁴ Ana-Maria Orbai,⁵ Fabian Proft,⁶ Alistair Reid,⁷ Maarten de Wit,⁸ Jérémy Lambert,⁹ Patrick Healy,¹⁰ Philip J. Mease¹¹ 

¹ Sorbonne Universite and Pitie-Salpetriere Hospital, Paris, France; ² University of Toronto, Schroeder Arthritis Institute, Krembil Research Institute, Toronto Western Hospital, Division of Rheumatology, Toronto, Canada; ³ Cleveland Clinic, Department of Rheumatic and Immunologic Diseases, Cleveland, Ohio, USA; ⁴Osaka Metropolitan University Graduate School of Medicine, Center for Senile Degenerative Disorders (CSDD), Osaka, Japan; ⁵ Johns Hopkins University School of Medicine, Division of Rheumatology, Baltimore, Maryland, USA; ⁶Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectiology and Rheumatology (including Nutrition Medicine), Berlin, Germany; ⁷ Wollongong Private Hospital (Part of Ramsay Health Care), University of Wollongong, Rheumatology, Wollongong, Australia; ⁸Stichting Tools, Patient Research Partner, Amsterdam, The Netherlands; ⁹UCB, Courbevoie, France; ¹⁰UCB, Morrisville, USA; ¹¹Providence-Swedish Medical Center and University of Washington, Department of Rheumatology, Seattle, USA.

Abstract or description:

Objective 

To assess whether achieving stringent treatment responses at Week 16 in bimekizumab (BKZ)-treated patients with active psoriatic arthritis (PsA) was associated with clinically meaningful improvements in patient-reported outcomes (PROs) over 3 years

Background

• PsA is a chronic inflammatory disease in which pain, fatigue and impaired functional capacity are among the most burdensome patient-reported symptoms, each contributing significantly to reduced health-related quality of life.1–3 

• Achieving an early and rapid response to treatment is an important goal to reduce symptoms and minimise disease impact.4,5 

• BKZ is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. 

Methods 

• BE OPTIMAL (NCT03895203) and BE COMPLETE (NCT03896581) were phase 3 trials, both placebo-controlled to Week 16, which assessed subcutaneous BKZ 160 mg every 4 weeks (Q4W), in patients with active PsA who were biologic disease-modifying antirheumatic drug (bDMARD)-naïve or had prior intolerance or inadequate response to tumour necrosis factor inhibitors (TNFi-IR), respectively. 

• Patients completing Week 52 in BE OPTIMAL or Week 16 in BE COMPLETE could enter BE VITAL (open-label extension; NCT04009499), where all patients received BKZ 160 mg Q4W. 

• In this post hoc analysis, BKZ-randomised patients were classified as rapid responders or non-responders based on achievement of resolution of swollen joint count (SJC=0) or ≥50% improvement from baseline in American College of Rheumatology response criteria (ACR50) at Week 16. 

• The proportion of BKZ-randomised patients reporting clinically meaningful improvements in the following PROs are presented to 3 years (Week 160/148 in BE OPTIMAL or Week 156 in BE COMPLETE), stratified by Week 16 SJC=0 or ACR50 response: – Pain50, defined as a substantial (≥50%) decrease from baseline in pain, measured by visual analogue scale (VAS; score range: 0 [no pain]–100 [most severe pain])6 – FACIT-Fatigue MCID (Functional Assessment of Chronic Illness Therapy-Fatigue minimal clinically important difference; score range 0–52 [higher scores indicate less fatigue]), defined as ≥4-point increase from baseline in patients with FACIT-Fatigue score ≤48 at baseline – PsAID-12 (12-item Psoriatic Arthritis Impact of Disease; score range: 0–10) no symptom or disease impact, defined as PsAID-12 total score ≤1.157 

• Data are reported as observed case (OC) or using modified non-responder imputation (mNRI). – mNRI considered all visits following discontinuation due to adverse events or lack of efficacy as non-response; all other missing data were imputed using multiple imputation and the response was derived from the imputed values. 

Results 

• 431 bDMARD-naïve and 267 TNFi-IR patients were randomised to BKZ in the BE OPTIMAL and BE COMPLETE studies, respectively. 

• At Week 16, SJC=0 was achieved by 48.3% of bDMARD-naïve patients and 45.9% of TNFi-IR patients (mNRI; Figure 1). At Week 16, ACR50 was achieved by 44.8% of bDMARD-naïve patients and 43.5% of TNFi-IR patients (mNRI; Figure 2). 

• Baseline characteristics were broadly comparable between responders and non-responders; responders were more likely overall to be younger and male (Table). 

• Across both bDMARD-naive and TNFi-IR patients, SJC=0 and ACR50 responders demonstrated greater improvements in PROs than non-responders at Week 16 (Figures 1–2). 

• Improvements in PROs in responders at Week 16 were sustained or increased further to Year 3 (Figures 1–2).

Conclusions 

Patients with PsA treated with bimekizumab who were SJC=0 or ACR50 responders at Week 16 demonstrated greater and sustained improvements in pain, fatigue and reduced disease impact over 3 years compared to non-responders, both in bDMARD-naïve and TNFi-IR patients. 

Interpretation should consider the post hoc design and potential confounding factors, including pain VAS being a component of the ACR response criteria. 

These data suggest that rapid and high clinical responses may lead to long-term improvements in PROs, reinforcing the importance of timely intervention with effective therapy for optimal PsA managemen